Aim: To identify the genes specifically expressed in human adult and fetal testes and spermatozoa. Methods: A human testis cDNA microarray was established. Then mRNAs of human adult and fetal testis and spermatozoa we...Aim: To identify the genes specifically expressed in human adult and fetal testes and spermatozoa. Methods: A human testis cDNA microarray was established. Then mRNAs of human adult and fetal testis and spermatozoa were purified and probes were prepared by a reverse transcription reaction with mRNA as the template. The microarray was hybridized with probes of adult and fetal testes and spermatozoa. The nucleic acid sequences of differentially expressed genes were determined and homologies were searched in the databases of GenBank. Results: A novel human testis-specific gene, PKH-T, was identified by hybridizing adult and fetal testis and spermatozoa probes with a human testis cDNA microarray. The cDNA of PKH-T was 1 069 bp in length. The cDNA sequence of this clone was deposited in the Genbank (AY303972) and PKH-T was also determined as Interim GenSymbol (Unigene, HS.38041). PKH-T contained most PKH conserved motif. The 239 amino acid sequences deduced from the 719 bp open reading frame (ORF) had a homology with the gene PKH (U89606). PKH-T was specifically and strongly expressed in the testis. Comparison of the differential expressions of PKH and PKH-T in testes of different develop-mental stages indicated that PKH-T was expressed in the adult testis and spermatozoa, while PKH, in the adult, fetal and aged testes. PKH-T had no expression in the testis of Sertoli cell only and partially spermatogenic arrest patients. Conclusion: PKH-T is a gene highly expressed in adult human testis and spermatozoa. It may play an important role in spermatogenesis and could be related to male infertility. (Asian J Androl 2004 Jun; 6: 83-91)展开更多
Pyridaben(PY)is a widely used organochlorine acaricide,which can be detected in the peripheral blood of pregnant women.Available evidence suggests that PY has reproductive toxicity.However,it remains uncertain whether...Pyridaben(PY)is a widely used organochlorine acaricide,which can be detected in the peripheral blood of pregnant women.Available evidence suggests that PY has reproductive toxicity.However,it remains uncertain whether prenatal PY exposure impacts neurobehavioral development in offspring.Here,we administered PY to pregnant mice at a dose of 0.5 and 5 mg kg^(-1)day^(-1)via gavage and observed anxietylike behaviors in PY offspring aged five weeks.We then integrated the metabolome and transcriptome of the offspring's brain to explore the underlying mechanism.Metabolome data indicated that the vitamin B6 metabolism pathway was significantly affected,and the pyridoxal 50-phosphate(PLP)concentration and the active form of vitamin B6 was significantly reduced.Moreover,the transcriptome data showed that both PLP generation-related Pdxk and anxiety-related Gad1 were significantly down-regulated.Meanwhile,there was a decreasing trend in the concentration of GABA in the hippocampal DG region.Next,we supplemented PLP at a dose of 20 mg kg^(-1)day^(-1)to the PY offspring via intraperitoneal injection at three weeks.We found up-regulated expression of Pdxk and Gad1 and restored anxiety-like behaviors.This study suggests that prenatal exposure to PY can disrupt vitamin B6 metabolism,reduce the concentration of PLP,down-regulate the expression levels of Pdxk and Gad1,inhibit the production of GABA,and ultimately lead to anxiety-like behaviors in offspring.展开更多
What is the most favorite and original chemistry developed in your research group? Vitamin B6-based biomimetic asymmetric catalysis. How do you get into this specific field? Could you please share some experiences wit...What is the most favorite and original chemistry developed in your research group? Vitamin B6-based biomimetic asymmetric catalysis. How do you get into this specific field? Could you please share some experiences with our readers? Enzymatic transformations are characterized by high efficiency, specific selectivities, and mild conditions, which attracts me to do some chemistry related to biological systems.展开更多
Huoxue Rongluo Tablet was made of tall gastrodis tuber, dahurian angelica root, honeysuckle stem, grassleaf sweetflag rhizome, common flowering quince fruit, figwort root, red peony root and peach seed at a ratio of 3...Huoxue Rongluo Tablet was made of tall gastrodis tuber, dahurian angelica root, honeysuckle stem, grassleaf sweetflag rhizome, common flowering quince fruit, figwort root, red peony root and peach seed at a ratio of 3:2:6:2:3:3:3:3. Huoxue Rongluo Tablet is a well-established and common pre- scription for the treatment of cerebral infarction. In this study, a rat model of cerebral ischemia was established and the animals were intragastrically administered Huoxue Rongluo Tablet. This treat- ment reduced infarct volume, decreased matrix metalloproteinase-9 expression, and improved neurological function. Moreover, the effects of Huoxue Rongluo Tablet were better than those of buflomedil pyridoxal phosphate. These results indicate that Huoxue Rongluo Tablet is effective in treating cerebral infarction by regulating matrix metalloproteinase-9 protein expression.展开更多
Colorectal cancer remains the third most common cancer in both women and men worldwide.Identifying modifiable dietary factors is crucial in developing primary prevention strategies.Vitamin B6 is involved in more than ...Colorectal cancer remains the third most common cancer in both women and men worldwide.Identifying modifiable dietary factors is crucial in developing primary prevention strategies.Vitamin B6 is involved in more than 100 coenzyme reactions,and may influence colorectal cancer risk in multiple ways including through its role in one-carbon metabolism related DNA synthesis and methylation and by reducing inflammation,cell proliferation,and oxidative stress.Observational studies of dietary or dietary plus supplementary intake of vitamin B6 and colorectal cancer risk have been inconsistent with most studies reporting nonsignificant positive or inverse associations.However,published studies of plasma pyridoxal 5'-phosphate(the active form of vitamin B6) levels consistently support an approximately 30%-50% reduction in risk of colorectal cancer comparing high with low concentrations.The reasons for the discrepancy in the results between dietary-based and plasma-based studies remain unresolved.Other unresolved questions include the effects of vitamin B6 intake in early life(i.e.,childhood or adolescence) and of suboptimal vitamin B6 status on colorectal cancer risk,whether the associations with vitamin B6 differ across molecular subtypes of colorectal cancer,and whether the vitamin B6-colorectal cancer association is modified by genetic variants of one-carbon metabolism.展开更多
Aminooxyacetate (AOA) is a pyridoxal phosphate antagonist that inhibits various plant enzymes (including transaminases) which require pyridoxal phosphate as a cofactor and it exhibits phytotoxic and herbicidal propert...Aminooxyacetate (AOA) is a pyridoxal phosphate antagonist that inhibits various plant enzymes (including transaminases) which require pyridoxal phosphate as a cofactor and it exhibits phytotoxic and herbicidal properties. We examined AOA and its analog, </span><i><span style="font-family:Verdana;">N</span></i><span style="font-family:Verdana;">-</span><i><span style="font-family:Verdana;">t</span></i><span style="font-family:Verdana;">-butoxycarbonyl-AOA (Boc-AOA) for phytotoxicity, interactions with weed pathogens (bioherbicides), and effects on an important pyridoxal requiring enzyme, cysteine synthase (CS, E.C. 4.2.99.8). Studies were performed on two weeds, </span><i><span style="font-family:Verdana;">i.e.</span></i><span style="font-family:Verdana;">, hemp sesbania [</span><i><span style="font-family:Verdana;">Sesbania exaltata</span></i><span style="font-family:Verdana;"> (Raf.) Rybd. Ex A.W. Hill] and sicklepod (</span><i><span style="font-family:Verdana;">Senna obtusifolia</span></i><span style="font-family:Verdana;">), and two pathogens, (</span><i><span style="font-family:Verdana;">Colletotrichum truncatum</span></i><span style="font-family:Verdana;"> and </span><i><span style="font-family:Verdana;">Alternaria cassiae</span></i><span style="font-family:Verdana;">), that are bioherbicidal agents against hemp sesbania and sicklepod, respectively. Pathogenicity tests, and assays for extractable, and </span><i><span style="font-family:Verdana;">in vitro </span></i><span style="font-family:Verdana;">CS activities were utilized. Phytotoxicity bioassays indicated that the bulky </span><i><span style="font-family:Verdana;">t</span></i><span style="font-family:Verdana;">-butoxycarbonyl moiety substitution on the AOA molecule did not substantially hinder expression of biological activity of Boc-AOA in these tests. Generally, spray application of the compounds to young dark-grown seedlings caused little growth effects, but root-feeding of the chemicals reduced growth (stem elongation) in both weeds. Hemp sesbania was generally more tolerant than sicklepod to these compounds. The only apparent positive interaction of the chemicals with these pathogens was the Boc-AOA:</span></span><span style="font-family:""> </span><i><span style="font-family:Verdana;">C. truncatum </span></i><span style="font-family:""><span style="font-family:Verdana;">combination treatment on hemp sesbania. Both compounds reduced extractable CS in the seedlings by 30%, 72 h after treatment. CS activity was reduced by 15% in hemp sesbania treated with </span><i><span style="font-family:Verdana;">C. truncatum</span></i><span style="font-family:Verdana;"> but increased 20% above control levels after infection of sicklepod by</span><i><span style="font-family:Verdana;"> A. cassiae</span></i><span style="font-family:Verdana;">. This latter effect suggests that CS may be involved in sicklepod defense mechanisms against this pathogen.展开更多
Xanthomonas oryzae pv.oryzicola(Xoc),which causes rice bacterial leaf streak,invades leaves mainly through stomata,which are often closed as a plant immune response against pathogen invasion.How Xoc overcomes stomatal...Xanthomonas oryzae pv.oryzicola(Xoc),which causes rice bacterial leaf streak,invades leaves mainly through stomata,which are often closed as a plant immune response against pathogen invasion.How Xoc overcomes stomatal immunity is unclear.Here,we show that the effector protein AvrRxo1,an ATPdependent protease,enhances Xoc virulence and inhibits stomatal immunity by targeting and degrading rice OsPDX1(pyridoxal phosphate synthase),thereby reducing vitamin B6(VB6)levels in rice.VB6 is required for the activity of aldehyde oxidase,which catalyzes the last step of abscisic acid(ABA)biosynthesis,and ABA positively regulates rice stomatal immunity against Xoc.Thus,we provide evidence supporting a model in which a major bacterial pathogen inhibits plant stomatal immunity by directly targeting VB6 biosynthesis and consequently inhibiting the biosynthesis of ABA in guard cells to open stomata.Moreover,AvrRxo1-mediated VB6 targeting also explains the poor nutritional quality,including low VB6 levels,of Xoc-infected rice grains.展开更多
The redox cofactor𝛽-nicotinamide adenine dinucleotide(NAD)has been revealed to serve as a building block for the biosynthesis of an alkaloid natural product,altemicidin.The biosynthetic pathway investigation i...The redox cofactor𝛽-nicotinamide adenine dinucleotide(NAD)has been revealed to serve as a building block for the biosynthesis of an alkaloid natural product,altemicidin.The biosynthetic pathway investigation identified a unique pyridoxal pyrophosphate(PLP)-dependent enzyme that utilizes NAD and S-adenosylmethionine(SAM)to build the bicyclic alkaloid scaffold,opening the door for biosynthetic studies of NAD-derived natural products.展开更多
文摘Aim: To identify the genes specifically expressed in human adult and fetal testes and spermatozoa. Methods: A human testis cDNA microarray was established. Then mRNAs of human adult and fetal testis and spermatozoa were purified and probes were prepared by a reverse transcription reaction with mRNA as the template. The microarray was hybridized with probes of adult and fetal testes and spermatozoa. The nucleic acid sequences of differentially expressed genes were determined and homologies were searched in the databases of GenBank. Results: A novel human testis-specific gene, PKH-T, was identified by hybridizing adult and fetal testis and spermatozoa probes with a human testis cDNA microarray. The cDNA of PKH-T was 1 069 bp in length. The cDNA sequence of this clone was deposited in the Genbank (AY303972) and PKH-T was also determined as Interim GenSymbol (Unigene, HS.38041). PKH-T contained most PKH conserved motif. The 239 amino acid sequences deduced from the 719 bp open reading frame (ORF) had a homology with the gene PKH (U89606). PKH-T was specifically and strongly expressed in the testis. Comparison of the differential expressions of PKH and PKH-T in testes of different develop-mental stages indicated that PKH-T was expressed in the adult testis and spermatozoa, while PKH, in the adult, fetal and aged testes. PKH-T had no expression in the testis of Sertoli cell only and partially spermatogenic arrest patients. Conclusion: PKH-T is a gene highly expressed in adult human testis and spermatozoa. It may play an important role in spermatogenesis and could be related to male infertility. (Asian J Androl 2004 Jun; 6: 83-91)
基金supported by the National Key R&D Program of China(grant number 2021YFC2701100 and 2021YFC2701102)China-U.S.Program for Biomedical Collaborative Research(NSFCNIH)(grant number 81961128022)+1 种基金the National Natural Science Foundation of China(grant number 81903351)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Pyridaben(PY)is a widely used organochlorine acaricide,which can be detected in the peripheral blood of pregnant women.Available evidence suggests that PY has reproductive toxicity.However,it remains uncertain whether prenatal PY exposure impacts neurobehavioral development in offspring.Here,we administered PY to pregnant mice at a dose of 0.5 and 5 mg kg^(-1)day^(-1)via gavage and observed anxietylike behaviors in PY offspring aged five weeks.We then integrated the metabolome and transcriptome of the offspring's brain to explore the underlying mechanism.Metabolome data indicated that the vitamin B6 metabolism pathway was significantly affected,and the pyridoxal 50-phosphate(PLP)concentration and the active form of vitamin B6 was significantly reduced.Moreover,the transcriptome data showed that both PLP generation-related Pdxk and anxiety-related Gad1 were significantly down-regulated.Meanwhile,there was a decreasing trend in the concentration of GABA in the hippocampal DG region.Next,we supplemented PLP at a dose of 20 mg kg^(-1)day^(-1)to the PY offspring via intraperitoneal injection at three weeks.We found up-regulated expression of Pdxk and Gad1 and restored anxiety-like behaviors.This study suggests that prenatal exposure to PY can disrupt vitamin B6 metabolism,reduce the concentration of PLP,down-regulate the expression levels of Pdxk and Gad1,inhibit the production of GABA,and ultimately lead to anxiety-like behaviors in offspring.
基金the National Natural Science Foundation of China (Nos. 21672148, 21871181)the Ministry of Education of China (PCSIRT_IRT_16R49).
文摘What is the most favorite and original chemistry developed in your research group? Vitamin B6-based biomimetic asymmetric catalysis. How do you get into this specific field? Could you please share some experiences with our readers? Enzymatic transformations are characterized by high efficiency, specific selectivities, and mild conditions, which attracts me to do some chemistry related to biological systems.
基金supported by the Scientific Research Project of Traditional Chinese Medicine of Hunan Province Chinese Medicine Research Administration Bureau in China,No.201136
文摘Huoxue Rongluo Tablet was made of tall gastrodis tuber, dahurian angelica root, honeysuckle stem, grassleaf sweetflag rhizome, common flowering quince fruit, figwort root, red peony root and peach seed at a ratio of 3:2:6:2:3:3:3:3. Huoxue Rongluo Tablet is a well-established and common pre- scription for the treatment of cerebral infarction. In this study, a rat model of cerebral ischemia was established and the animals were intragastrically administered Huoxue Rongluo Tablet. This treat- ment reduced infarct volume, decreased matrix metalloproteinase-9 expression, and improved neurological function. Moreover, the effects of Huoxue Rongluo Tablet were better than those of buflomedil pyridoxal phosphate. These results indicate that Huoxue Rongluo Tablet is effective in treating cerebral infarction by regulating matrix metalloproteinase-9 protein expression.
文摘Colorectal cancer remains the third most common cancer in both women and men worldwide.Identifying modifiable dietary factors is crucial in developing primary prevention strategies.Vitamin B6 is involved in more than 100 coenzyme reactions,and may influence colorectal cancer risk in multiple ways including through its role in one-carbon metabolism related DNA synthesis and methylation and by reducing inflammation,cell proliferation,and oxidative stress.Observational studies of dietary or dietary plus supplementary intake of vitamin B6 and colorectal cancer risk have been inconsistent with most studies reporting nonsignificant positive or inverse associations.However,published studies of plasma pyridoxal 5'-phosphate(the active form of vitamin B6) levels consistently support an approximately 30%-50% reduction in risk of colorectal cancer comparing high with low concentrations.The reasons for the discrepancy in the results between dietary-based and plasma-based studies remain unresolved.Other unresolved questions include the effects of vitamin B6 intake in early life(i.e.,childhood or adolescence) and of suboptimal vitamin B6 status on colorectal cancer risk,whether the associations with vitamin B6 differ across molecular subtypes of colorectal cancer,and whether the vitamin B6-colorectal cancer association is modified by genetic variants of one-carbon metabolism.
文摘Aminooxyacetate (AOA) is a pyridoxal phosphate antagonist that inhibits various plant enzymes (including transaminases) which require pyridoxal phosphate as a cofactor and it exhibits phytotoxic and herbicidal properties. We examined AOA and its analog, </span><i><span style="font-family:Verdana;">N</span></i><span style="font-family:Verdana;">-</span><i><span style="font-family:Verdana;">t</span></i><span style="font-family:Verdana;">-butoxycarbonyl-AOA (Boc-AOA) for phytotoxicity, interactions with weed pathogens (bioherbicides), and effects on an important pyridoxal requiring enzyme, cysteine synthase (CS, E.C. 4.2.99.8). Studies were performed on two weeds, </span><i><span style="font-family:Verdana;">i.e.</span></i><span style="font-family:Verdana;">, hemp sesbania [</span><i><span style="font-family:Verdana;">Sesbania exaltata</span></i><span style="font-family:Verdana;"> (Raf.) Rybd. Ex A.W. Hill] and sicklepod (</span><i><span style="font-family:Verdana;">Senna obtusifolia</span></i><span style="font-family:Verdana;">), and two pathogens, (</span><i><span style="font-family:Verdana;">Colletotrichum truncatum</span></i><span style="font-family:Verdana;"> and </span><i><span style="font-family:Verdana;">Alternaria cassiae</span></i><span style="font-family:Verdana;">), that are bioherbicidal agents against hemp sesbania and sicklepod, respectively. Pathogenicity tests, and assays for extractable, and </span><i><span style="font-family:Verdana;">in vitro </span></i><span style="font-family:Verdana;">CS activities were utilized. Phytotoxicity bioassays indicated that the bulky </span><i><span style="font-family:Verdana;">t</span></i><span style="font-family:Verdana;">-butoxycarbonyl moiety substitution on the AOA molecule did not substantially hinder expression of biological activity of Boc-AOA in these tests. Generally, spray application of the compounds to young dark-grown seedlings caused little growth effects, but root-feeding of the chemicals reduced growth (stem elongation) in both weeds. Hemp sesbania was generally more tolerant than sicklepod to these compounds. The only apparent positive interaction of the chemicals with these pathogens was the Boc-AOA:</span></span><span style="font-family:""> </span><i><span style="font-family:Verdana;">C. truncatum </span></i><span style="font-family:""><span style="font-family:Verdana;">combination treatment on hemp sesbania. Both compounds reduced extractable CS in the seedlings by 30%, 72 h after treatment. CS activity was reduced by 15% in hemp sesbania treated with </span><i><span style="font-family:Verdana;">C. truncatum</span></i><span style="font-family:Verdana;"> but increased 20% above control levels after infection of sicklepod by</span><i><span style="font-family:Verdana;"> A. cassiae</span></i><span style="font-family:Verdana;">. This latter effect suggests that CS may be involved in sicklepod defense mechanisms against this pathogen.
基金This study was supported by the National Natural Science Foundation(31872925 and 32072500)Natural Science Outstanding Youth Fund of Shandong Province(JQ201807)+3 种基金Shandong Province Key Research and Development Plan(2019JZZY020608,2020CXGC010803,and 2019GN C106152)Science and Technology Support Plan for Youth Innovation of Colleges and Universities of Shandong Province(2019KJF023)the National Key Research and Development Program of China(2016YFD0100903)X.D.thanks S.H.for hosting his research visit at Mich-igan State University,supported by the United States National Institute of General Medical Sciences(GM109928).
文摘Xanthomonas oryzae pv.oryzicola(Xoc),which causes rice bacterial leaf streak,invades leaves mainly through stomata,which are often closed as a plant immune response against pathogen invasion.How Xoc overcomes stomatal immunity is unclear.Here,we show that the effector protein AvrRxo1,an ATPdependent protease,enhances Xoc virulence and inhibits stomatal immunity by targeting and degrading rice OsPDX1(pyridoxal phosphate synthase),thereby reducing vitamin B6(VB6)levels in rice.VB6 is required for the activity of aldehyde oxidase,which catalyzes the last step of abscisic acid(ABA)biosynthesis,and ABA positively regulates rice stomatal immunity against Xoc.Thus,we provide evidence supporting a model in which a major bacterial pathogen inhibits plant stomatal immunity by directly targeting VB6 biosynthesis and consequently inhibiting the biosynthesis of ABA in guard cells to open stomata.Moreover,AvrRxo1-mediated VB6 targeting also explains the poor nutritional quality,including low VB6 levels,of Xoc-infected rice grains.
基金supported by the National Natural Science Foundation of China(22177092,82003631)the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang(2020R01004)to L.Z.
文摘The redox cofactor𝛽-nicotinamide adenine dinucleotide(NAD)has been revealed to serve as a building block for the biosynthesis of an alkaloid natural product,altemicidin.The biosynthetic pathway investigation identified a unique pyridoxal pyrophosphate(PLP)-dependent enzyme that utilizes NAD and S-adenosylmethionine(SAM)to build the bicyclic alkaloid scaffold,opening the door for biosynthetic studies of NAD-derived natural products.